Experiments in this laboratory show that the mechanism of action of parathyroid hormone is mediated through activation of adenylate cyclase in bone and kidney. An observation related to this mechanism is that parathyroid hormone causes a rapid, marked rise in urinary excretion of cyclic 3',5'AMP in normal subjects. Recent studies show that this response is absent in pseudohypoparathyroidism. In addition, it has been found that parathyroid hormone is indeed secreted in this disorder and that secretion of endogenous hormone can be suppressed by hypercalcemia. These several findings have led to the conclusion that the cause of pseudohypoparathyroidism may be the existence of genetically deficient or defective adenylate cyclase in the bone and kidney of these subjects. It was also observed that the urinary cyclic AMP response to parathyroid hormone is a better diagnostic index of pseudohypoparathyroidism than measurements of phosphage clearance used heretofore.